P-selectin glycoprotein ligand-1-deficient mice have impaired leukocyte tethering to E-selectin under flow.
P-selectin glycoprotein ligand-1-deficient mice have impaired leukocyte tethering to E-selectin under flow.
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P-选择素糖蛋白配体1缺陷的小鼠在流动下白细胞与E-选择素的束缚受损。
DOI：
10.1172/jci14151
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
McEver,RodgerP
中科院分区：
文献类型：
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作者：
Xia,Lijun;Sperandio,Markus;Yago,Tadayuki;McDaniel,JMichael;Cummings,RichardD;Pearson-White,Sonia;Ley,Klaus;McEver,RodgerP
P-选择素糖蛋白配体-1(PSGL-1)在血流状态下介导白细胞对P-选择素的滚动。使白细胞与E-选择素结合或在E-选择素上滚动的糖蛋白尚不清楚。我们使用基因打靶技术来制备PSGL-1缺陷(PSGL-1-/-)小鼠，这些小鼠是健康的，但总白细胞适度升高。流体相E-选择素与PSGL-1-/-比PSGL-1+/+中性粒细胞结合的部位少约70%。与PSGL-1+/+白细胞相比，PSGL-1-/-白细胞在体外滚动到E-选择素上的细胞明显减少，因为它们最初与E-选择素的结合受到了损害。被拴住的残余细胞以与PSGL-1+/+白细胞相同的剪切阻力和速度滚动。与PSGL-1+/+小鼠相比，经肿瘤坏死因子-α处理的提睾肌小静脉中，P-选择素功能被单抗阻断的PSGL-1-/-白细胞显著减少。被拴住的残留PSGL-1-/-白细胞以相当于PSGL-1+/+白细胞的慢速度滚动。这些结果揭示了PSGL-1在流动状态下将白细胞与E-选择素捆绑在一起的新功能。
P-selectin glycoprotein ligand-1 (PSGL-1) mediates rolling of leukocytes on P-selectin under flow. The glycoproteins that enable leukocyte tethering to or rolling on E-selectin are not known. We used gene targeting to preparePSGL-1–deficient (PSGL-1–/–) mice, which were healthy but had moderately elevated total blood leukocytes. Fluid-phase E-selectin bound to approximately 70% fewer sites onPSGL-1–/–thanPSGL-1+/+neutrophils. Compared withPSGL-1+/+leukocytes, significantly fewerPSGL-1–/–leukocytes rolled on E-selectin in vitro, because their initial tethering to E-selectin was impaired. The residual cells that tethered rolled with the same shear resistance and velocities asPSGL-1+/+leukocytes. Compared withPSGL-1+/+mice, significantly fewerPSGL-1–/–leukocytes rolled on E-selectin in TNF-α–treated venules of cremaster muscle in which P-selectin function was blocked by an mAb. The residualPSGL-1–/–leukocytes that tethered rolled with slow velocities equivalent to those ofPSGL-1+/+leukocytes. These results reveal a novel function for PSGL-1 in tethering leukocytes to E-selectin under flow.